Dietary sodium depletion in man is followed by rapid conservation of sodium by the kidneys. The rapidity of the response suggests that the gastrointestinal tract is involved in the early recognition of changes of sodium load presented to the body and in the regulation of sodium excretion. In a pilot study to test this hypothesis in man, normal volunteer subjects were placed on a sodium deficient diet for five days at which time sodium balance was achieved. When the subjects were subsequently repleted with an oral sodium load, they excreted more sodium than when they received the same sodium load intravenously. The differences were statistically significant at eight, twelve and twenty-four hours after sodium repletion. This constitutes evidence that there is a receptor mechanism for sodium in the gastrointestinal tract which regulates urinary sodium excretion. During the past year, the rabbit has been established as a valid experimental animal model for this mechanism. Using this model it has been shown that the high level of sodium excretion after gastrointestinal sodium loading is not dependent on changes in levels of endogenous aldosterone. Parallel studies are currently being conducted in normal and adrenal-insufficient human volunteers. During the coming year, the proposed work will develop the concept of a gastrointestinal sodium input monitor through studies to determine its anatomic site, specificity, and physiologic mechanism. These studies will involve normal human volunteers and volunteer patients, experimental animals, and laboratory methods such as urinary electrolytes, creatinine and aldosterone measurements.